Interaction of hyperalgesia and sensory loss in complex regional pain syndrome type I (CRPS I)

Abstract

Background: Sensory abnormalities are a key feature of Complex Regional Pain Syndrome (CRPS). In order to characterise these changes in patients suffering from acute or chronic CRPS I, we used Quantitative Sensory Testing (QST) in comparison to an age and gender matched control group.

Methods: 61 patients presenting with CRPS I of the upper extremity and 56 healthy subjects were prospectively assessed using QST. The patients' warm and cold detection thresholds (WDT; CDT), the heat and cold pain thresholds (HPT; CPT) and the occurrence of paradoxical heat sensation (PHS) were observed.

Results: In acute CRPS I, patients showed warm and cold hyperalgesia, indicated by significant changes in HPT and CPT. WDT and CDT were significantly increased as well, indicating warm and cold hypoaesthesia. In chronic CRPS, thermal hyperalgesia declined, but CDT as well as WDT further deteriorated. Solely patients with acute CRPS displayed PHS. To a minor degree, all QST changes were also present on the contralateral limb.

Conclusions: We propose three pathomechanisms of CRPS I, which follow a distinct time course: Thermal hyperalgesia, observed in acute CRPS, indicates an ongoing aseptic peripheral inflammation. Thermal hypoaesthesia, as detected in acute and chronic CRPS, signals a degeneration of A-delta and C-fibres, which further deteriorates in chronic CRPS. PHS in acute CRPS I indicates that both inflammation and degeneration are present, whilst in chronic CRPS I, the pathomechanism of degeneration dominates, signalled by the absence of PHS. The contralateral changes observed strongly suggest the involvement of the central nervous system.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Duration of disease in patients with acute and chronic CRPS. No intersection between both groups occurred.

Figure 2. Thermal detection in acute and chronic CRPS.

Cold detection thresholds (A) and warm detection thresholds (B), shown as change (Δ°C) from the adaption temperature of 32°C. Thresholds are significantly increased in acute and chronic CRPS. Significant increases are also found in the contralateral “unaffected” hand. Significance vs. controls: ** p++ p<0.01, +++ p<0.001; Significance vs. ipsilateral hand: (§) p<0.10, § p<0.05, §§§ p<0.001. Note: Significance marks that bridge symbols of ipsilateral and contralateral hands apply to both hands. Error bars show 1SEM.

Figure 3. Thermal pain thresholds in acute and chronic CRPS.

Cold pain thresholds (A) and heat pain thresholds (B) are significantly lowered in acute CRPS (corresponding to cold and heat hyperalgesia). Pain partially (cold pain) or totally (heat pain) recovers to normal in chronic CRPS. Significant increases of similar magnitude are also found in the contralateral “unaffected” hand for heat pain (B) and to a lesser extent in cold pain (A). Significance vs. controls: *** p+++ p<0.001; Significance vs. ipsilateral hand: (§) p<0.10, § p<0.05. Note: Significance marks that bridge symbols of ipsilateral and contralateral hands apply to both hands. Error bars show 1SEM.

Figure 4. Standardised comparison of QST data normalised to mean and standard deviation of the control group (z-normalisation).

Normalised data show a severe sensory loss in acute CRPS for all thermal detection parameters (CDT, WDT, TSL) in the affected ipsilateral hand (>1 SD of controls), but also a moderate loss in the contralateral hand, which aggravates in chronic CRPS. In contrast, there is a substantial gain in thermal nociception (CPT, HPT) in acute CRPS (hyperalgesia), equally expressed in both hands (≈1 SD of controls). Heat hyperalgesia almost fully subsides in chronic CRPS, while significant cold hyperalgesia is retained. For the sake of clarity there are no symbols of statistical significance in this figure (c.f. respective paragraph in results).

Figure 5. (A) Paradoxical heat sensation (PHS) to mild cold stimuli as elicited by alternating cold and warm stimulation (TSL).

PHS was a frequent finding in both hands in acute CRPS, and fully subsided in the chronic phase. Significance vs. controls: *** p+++ p<0.001; Significance vs. ipsilateral hand: (§) p<0.10, § p<0.05. Note: Significance marks that bridge symbols of ipsilateral and contralateral hands apply to both hands. (B) PHS-positive CRPS patients (PHS+) exhibited a significantly more pronounced cold hyperalgesia than PHS-negative CRPS patients (PHS−). In contrast, there was no such difference in heat hyperalgesia. Error bars show 1SEM.